Rapamycin and cyclosporine have different effects on expression of Ang-1 and Ang-2 and Tie2 in rat renal allograft with chronic allograft nephropathy.
OBJECTIVE
Previous studies have indicated that angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) and tyrosine kinase receptor Tie2 regulate the maintenance and integrity of blood vessels and have potential anti-inflammatory properties. This study of cardiac allografts investigated whether there is a difference between rapamycin and cyclosporine A (CsA) in the ability to affect expression of Ang1, Ang2, and Tie2 in rat renal allografts with chronic allograft nephropathy (CAN).


METHODS
A male inbred F344 to Lewis rat renal CAN model was established via a modified Kamada procedure. The recipients were first treated with CsA, 10 mg/kg/d, for 10 days and then allocated randomly to three oral treatment groups: control; CsA, 6 mg/kg/d; and rapamycin, 0.8 mg/kg/d. At 4, 8, and 12 weeks posttransplantation, the rats were killed to harvest the renal allografts. The serum creatinine concentration (SCr) was measured, and the pathologic changes were assessed according to Banff 97 criteria. The expression of messengerRNA and proteins of Ang1, Ang2, and Tie2 was determined using real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry.


RESULTS
The elevation of SCr and the pathologic changes of CAN were observed in the control and CsA groups at 8 and 12 weeks; the differences between the 2 groups were not significant (P > .05). The levels of SCr and Banff score in the rampamycin group were lower than those in other 2 groups (P < .01). The expression of Ang1 and Ang2 was localized to epithelial cells and endothelium of vascular bundles of glomeruli, and Tie2 was specifically expressed in the endothelium of vessels in all 3 groups. At 4 weeks, the differences in mRNA expression of Ang1, Ang2, and Tie2 between 3 groups were not significant (P > .05). In a comparison of the control and CsA groups, mRNA expression of Ang1 was increased (P < .05), and mRNA expression of Ang2 and Tie2 was decreased (P < .05) in the rapamycin group at 8 and 12 weeks. The differences between the control and CsA groups were not significant at 8 or 12 weeks (P > .05).


CONCLUSIONS
Our results show that compared with CsA, rapamycin modulates the expression of Ang1, Ang2, and Tie2 in rat renal allografts with CAN, which suggests that rapamycin may improve the long-term survival of renal allografts through its vasculoprotective properties.
Ma
X
X
Transplantation Institute, West China Hospital, Sichuan University, Chengdu, China.
Lu
Y P
YP
Yang
L
L
Song
J
J
Luo
G H
GH
Shi
Y J
YJ
Li
Y P
YP
D042683:Angiopoietin-1 / Q000235:genetics*; D042702:Angiopoietin-2 / Q000235:genetics*; D000818:Animals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D042787:Receptor, TIE-2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D017931:DNA Primers; D012333:RNA, Messenger; D016572:Cyclosporine; D003404:Creatinine; D042787:Receptor, TIE-2; D020123:Sirolimus